Direct Puncture of the Superficial Temporal Artery in Embolization of a Scalp Arteriovenous Fistula: A Case Report.

We describe a minimally invasive endovascular approach to treat an arteriovenous fistula of the scalp. We performed a direct puncture of the lesion through the patient's scalp for liquid embolic agent injection along with external compression of the superficial temporal artery to perform a "manual pressure-cooker technique." The combination of these minimally invasive techniques resulted in an excellent clinical and radiographic outcome.

Progressive Myelopathy With Acute Worsening After Steroids and Lumbar Puncture.

We present the case of a 73-year-old woman with a 3-month history of non-traumatic thoracic myelopathy. Initial MRI showed a T6-conus T2 signal hyperintensity. Based on this presentation, and given a personal and family history of autoimmune disease, our patient was first managed as an inflammatory transverse myelitis.

Separating the Wheat from the Chaff: The Use of Upstream Regulator Analysis to Identify True Differential Expression of Single Genes within Transcriptomic Datasets.

The development of DNA microarray and RNA-sequencing technology has led to an explosion in the generation of transcriptomic differential expression data under a wide range of biologic systems including those recapitulating the monogenic muscular dystrophies. Data generation has increased exponentially due in large part to new platforms, improved cost-effectiveness, and processing speed. However, reproducibility and thus reliability of data remain a central issue, particularly when resource constraints limit experiments to single replicates.

Association between insulin resistance and post-ischaemic stroke outcome in patients without diabetes: protocol for a systematic review and meta-analysis.

Introduction: Insulin resistance is an independent risk factor for atherosclerosis, coronary artery disease and ischaemic stroke. Currently, insulin resistance is not usually included in post-stroke risk stratification. This systematic review and meta-analysis intends to determine if available scientific knowledge supports an association between insulin resistance and post-stroke outcomes in patients without diabetes.

Pharmacologic normalization of pathogenic dosage underlying genetic diseases: an overview of the literature and path forward.

Most monogenic disorders are caused by a pathologic deficit or excess of a single transcript and/or protein. Given that small molecules, including drugs, can affect levels of mRNA and protein, the pharmacologic normalization of such pathogenic dosage represents a possible therapeutic approach for such conditions. Here, we review the literature exploring pharmacologic modulation of mRNA and/or protein levels for disorders with paralogous modifier genes, for haploinsufficient disorders (insufficient gene-product), as well as toxic gain-of-function disorders (surplus or pathologic gene-product).

Transcriptomic RNAseq drug screen in cerebrocortical cultures: toward novel neurogenetic disease therapies.

Rare monogenic diseases affect millions worldwide; although over 4500 rare disease genotypes are known, disease-modifying drugs are available for only 5% of them. The sheer number of these conditions combined with their rarity precludes traditional costly drug discovery programs. An economically viable alternative is to repurpose established drugs for rare diseases.

Anisomycin Activates Utrophin Upregulation Through a p38 Signaling Pathway.

Duchenne muscular dystrophy is a recessive X-linked disease characterized by progressive muscle wasting; cardiac or respiratory failure causes death in most patients by the third decade.  The disease is caused by mutations in the dystrophin gene that lead to a loss of functional dystrophin protein. Although there are currently few treatments for Duchenne muscular dystrophy, previous reports have shown that upregulating the dystrophin paralog utrophin in Duchenne muscular dystrophy mouse models is a promising therapeutic strategy.

Mining the transcriptome for rare disease therapies: a comparison of the efficiencies of two data mining approaches and a targeted cell-based drug screen.

Most monogenic diseases can be viewed as conditions caused by dysregulated protein activity; therefore, drugs can be used to modulate gene expression, and thus protein level, possibly conferring clinical benefit. When considering repurposing drugs for loss of function diseases, there are three classes of genetic disease amenable to an increase of function; haploinsufficient dominant diseases, those secondary to hypomorphic recessive alleles, and conditions with rescuing paralogs. This therapeutic model then brings the questions: how frequently do such clinically useful drug-gene interactions occur and what is the most rapid and efficient route by which to identify them.

Sodium Channel Inhibitors Reduce DMPK mRNA and Protein.

Myotonic dystrophy type 1 (DM1) is caused by an expanded trinucleotide (CTG)n tract in the 3' untranslated region (UTR) of the dystrophia myotonica protein kinase (DMPK) gene. This results in the aggregation of an expanded mRNA forming toxic intranuclear foci which sequester splicing factors. We believe down-regulation of DMPK mRNA represents a potential, and as yet unexplored, DM1 therapeutic avenue.

VPAC2 receptor agonist BAY 55-9837 increases SMN protein levels and moderates disease phenotype in severe spinal muscular atrophy mouse models.

Background: Spinal Muscular Atrophy (SMA) is one of the most common inherited causes of infant death and is caused by the loss of functional survival motor neuron (SMN) protein due to mutations or deletion in the SMN1 gene. One of the treatment strategies for SMA is to induce the expression of the protein from the homologous SMN2 gene, a rescuing paralog for SMA.

Methods And Results: Here we demonstrate the promise of pharmacological modulation of SMN2 gene by BAY 55-9837, an agonist of the vasoactive intestinal peptide receptor 2 (VPAC2), a member of G protein coupled receptor family.

Celecoxib increases SMN and survival in a severe spinal muscular atrophy mouse model via p38 pathway activation.

The loss of functional Survival Motor Neuron (SMN) protein due to mutations or deletion in the SMN1 gene causes autosomal recessive neurodegenerative spinal muscle atrophy (SMA). A potential treatment strategy for SMA is to upregulate the amount of SMN protein originating from the highly homologous SMN2 gene, compensating in part for the absence of the functional SMN1 gene. We have previously shown that in vitro activation of the p38 pathway stabilizes and increases SMN mRNA levels leading to increased SMN protein levels.

Prolactin increases SMN expression and survival in a mouse model of severe spinal muscular atrophy via the STAT5 pathway.

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that is characterized by the loss of motor neurons, resulting in progressive muscle atrophy. It is caused by the loss of functional survival motor neuron (SMN) protein due to mutations or deletion in the SMN1 gene. A potential treatment strategy for SMA is to upregulate levels of SMN protein.